Molecular Medicine Unit, UCL-Institute of Child Health, London WC1N 1EH, UK.
Cardiovasc Res. 2011 Jul 15;91(2):260-8. doi: 10.1093/cvr/cvr035. Epub 2011 Jan 31.
As the developing heart grows and the chamber walls thicken, passive diffusion of oxygen and nutrients is replaced by a vascular plexus which remodels and expands to form a mature coronary vascular system. The coronary arteries and veins ensure the continued development of the heart and facilitate cardiac output with progression towards birth. Many aspects of coronary vessel development are surprisingly not well understood and recently there has been much debate surrounding both the developmental origin and tissue contribution of cardiovascular cells alongside the specific signals that determine their fate and function. What is clear is that an understanding of the cellular and molecular cues to vascularize the heart of the embryo has significant implications for adult heart disease and regeneration, as we move towards targeted cell-based therapies for neovascularization and coronary bypass engraftment. This review will focus on the proposed cellular origins for the coronary endothelium with due consideration to the pro-epicardial organ/epicardium, sinus venosus and endocardium as potential sources, and we will explore the outstanding questions and technical limitations with respect to accurate labelling and lineage tracing of the developing coronaries. We will briefly document canonical vascular signalling that induces vessels in the heart alongside a focus on the potential for developmental reprogramming and putative mechanisms underpinning venous vs. arterial cell fate. Finally, we will extrapolate directly from development to address adult maintenance of the coronaries, vascular homeostasis and remodelling in response to pathology, aligned with the potential for revascularizing the injured adult heart.
随着心脏的生长和心室壁的增厚，氧气和营养物质的被动扩散被一个血管丛所取代，这个血管丛会重塑和扩张，形成一个成熟的冠状动脉系统。冠状动脉和静脉确保了心脏的持续发育，并促进了心脏输出，以促进分娩。冠状动脉血管发育的许多方面出人意料地还没有被很好地理解，最近围绕着心血管细胞的发育起源和组织贡献，以及决定它们命运和功能的特定信号，一直存在很多争论。显而易见的是，对胚胎心脏血管化的细胞和分子线索的理解，对成人心脏病和再生具有重要意义，因为我们正在朝着针对血管新生和冠状动脉旁路移植的基于细胞的靶向治疗方法迈进。这篇综述将重点讨论冠状动脉内皮的拟议细胞起源，并适当考虑心外膜/心外膜、窦静脉和心内膜作为潜在的来源，我们将探讨关于发育中的冠状动脉进行准确标记和谱系追踪的悬而未决的问题和技术限制。我们将简要记录诱导心脏血管生成的经典血管信号，同时关注发育重编程的潜力和潜在的静脉与动脉细胞命运的机制。最后，我们将直接从发育推断到成年期的冠状动脉维持、血管稳态和对病理的重塑，与使受伤的成年心脏再血管化的潜力相一致。
